Lower 1-year LDL-c after revascularization reduces MACCE in T2DM and CHD
Influence of LDL-Cholesterol Lowering on Cardiovascular Outcomes in Patients With Diabetes Mellitus Undergoing Coronary Revascularization
Introduction and methods
For management of patients with coronary heart disease (CHD) and T2DM, guidelines recommend intensive lifestyle changes together with aggressive, multifactorial secondary prevention, consisting of optimal medical therapy (OMT) and most appropriate revascularization strategy . Coronary artery bypass grafting (CABG) added to OMT has demonstrated to lower major adverse cardiac or cerebrovascular events (MACCE) compared to OMT alone  or percutaneous coronary intervention (PCI) plus OMT  in patients with T2DM and stable CHD in need of revascularization.
Despite this clear recommendations, there is limited knowledge on impact of LDL-c reduction following revascularization in patients with T2DM. Therefore, this study investigated the influence of LDL-c levels at 1 year follow-up following a coronary revascularization procedure on incidence of long-term MACCE in patients with T2DM. More specifically, it was assessed whether there was a graded effect of achieved LDL-c on outcomes and whether there was a differential effect of LDL-c reduction according to assigned intervention strategy (revascularization with PCI, CABG or OMT alone).
Patient-level data from 3 large randomized trials of coronary revascularization were pooled (BARI 2D, COURAGE and FREEDOM [2-4]). The study population consisted of 4050 patients. Patients were categorized according achieved LDL-c levels after the first year of follow-up (<70 mg/dL [n=1398, 34.5%]; 70 and <100 mg/dL [n=1711, 42.2%]; and ≥100 mg/dL [n=941, 23.2%]).1348 Patients (33.3%) were assigned to OMT group, 990 (24.4%) to CABG plus OMT and 1712 (42.3%) to PCI plus OMT. Primary outcome was 4-year rate of the MACCE composite: all-cause mortality, nonfatal MI or nonfatal stroke. Subsequent revascularization was a secondary endpoint. Median follow-up in the pooled cohort was 3.9 years (Q1 to Q3: 3.0-4.0) after the 1-year assessment.
- Patients with 1- year LDL-c ≥100 mg/dL had higher 4-year risk of MACCE compared to those with 1- year LDL-c 70 and <100 mg/dL and those with LDL-c <70 mg/dL (17.2% vs. 13.3% and 13.1%, respectively, P=0.016).
- In regression analysis, compared to patients with 1- year LDL-c <70 mg/dL, MACCE was higher in patients with 1-year LDL-c ≥100 mg/dL (HR 1.46, 95%CI: 1.15-1.85, P=0.002) and similar in those with 1-year LDL-c between 70 and <100 mg/dL (HR 1.97, 95%CI: 0.86-1.32, P=0.54).
- When 1-year LDL-c was used a continuous variable, each 10 mg/dL increase in 1-year LDL-c resulted in 4% increase in risk of MACCE over the 4-year follow-up (HR 1.04, 95%CI: 1.01 to 1.07, P=0.017).
- Compared to OMT, CABG was associated with lower rates of MACCE, regardless of 1-year LDL-c strata.
- PCI patients with 1- year LDL-c <70 mg/dL had lower rate of MACCE compared to patients with OMT (HR 0.61, 95%CI: 0.40-0.91, P=0.016). This effect was not observed for the other LDL-c strata.
- CABG patients had lower rates of MACCE compared to PCI patients in those with 1-year LDL-c between 70 and <100 mg/dL (HR 0.49, 95%CI: 0.31-0.79, P=0.003) and 1-year LDL-c ≥100 mg/dL (HR 0.53, 95%CI: 0.30-0.91, P=0.022). No difference was observed in patients with 1-year LDL-c <70 mg/dL.
- No differences in subsequent revascularization were observed when comparing patients with 1- year LDL-c between 70 and <100 mg/dL with LDL-c <70 mg/dL, whereas a nonsignificant trend was observed when comparing 1-year LDL-c ≥100 mg/dL with <70 mg/dL (HR 1.24, 95%CI: 0.99-1.56, P=0.066).
- CABG was associated with lower rates of subsequent revascularization compared to OMT and PCI in all 1-year LDL-c strata. No difference in subsequent revascularization rates was observed when comparing PCI with OMT for all 1-year LDL-c strata.
This analysis of pooled data from 3 trials demonstrated that T2DM patients undergoing revascularization with achieved 1-year LDL-c levels ≥100 mg/dL had higher 4-year risk of MACCE and likely higher risk of revascularization compared to patients with LDL-c <70 mg/dL, showing the importance of LDL-c control in the first years after revascularization procedure. In T2DM patients undergoing PCI LDL-c lowering is important, because when compared to OMT alone, reduction of MACCE was only observed in those with 1-year LDL-c <70 mg/dL. CABG was superior to OMT for all LDL-c strata and CABG was superior to PCI for LDL-c strata >70 mg/dL.